Stimuli-responsive Carriers for Controlled Intracellular Drug Release

Stimuli-responsive carriers are a class of drug delivery systems which can change their physicochemical properties and/or structural conformations in response to specific stimuli. Although passive and active drug targeting has proved to reduce the side effects to normal cells, controlled intracellular drug release should be included in drug carriers to enhance the bioavailability of drugs at the disease site.This review focuses on several recent advances in the development of stimuli-responsive carriers for spatially and temporally controlled release of therapeutic agents in response to intracellular stimuli, such as pH, redox potential, reactive oxygen species, enzyme and temperature.Among the different types of stimuli, pH-responsive carriers have been mostly used to design intracellular controlled release system. The sharp difference of redox potential between inside and outside cells is attributed to the high variation in concentration of glutathione. ROS-responsive carriers are gaining much attention for selective release of therapeutic agents by sensing oxidative conditions at different levels. The advantages of utilizing enzymes as the trigger of stimuli-responsive carriers include diverse types of enzymes, high selectivity of enzyme catalyzed reactions and the mild reaction conditions involved. Abnormal temperature is another unique stimulus and has been widely used to trigger controlled release of drug in tumor cells.Recent developments highlighted in this paper demonstrate that stimuli-responsive carriers possess great potential as a new platform for controlled intracellular drug release.